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Title | Regulated nuclear entry of over-expressed Setdb1 |
Authors | Sun Hwa Cho; Jung Sun Park; Yong-Kook Kang |
Publisher | Wiley-Blackwell |
Issue Date | 2013 |
Citation | Genes to Cells, vol. 18, no. 8, pp. 694-703 |
Abstract | Setdb1 is a histone H3-lysine 9 (H3K9)-specific methyltransferase that interacts with various transcriptional regulators to induce local heterochromatin formation and participates as an indispensable component in building promyelocytic leukemia nuclear body (PML-NB), which is involved in various biological processes. We studied the effects of Setdb1 over-expression. We unexpectedly observed that exogenously expressed GFP-Setdb1 was retained in the cytoplasm, whereas endogenous Setdb1 showed a punctate nuclear signal. Leptomycin B (LMB) treatment, which blocks protein export from the nucleus, showed that entry of GFP-Setdb1 to the nucleus was regulated and that GFP-Setdb1 in the nucleus could localize at PML-NB as endogenous Setdb1. An analysis of Setdb1 deletion constructs showed that the N-terminal region was related to the nuclear export of Setdb1; supporting this, we detected two nuclear export signal motifs in this region. This N-terminal region had a SUMO interaction motif (SIM) whose mutation greatly reduced the ability of Setdb1 to associate with PML-NB and thus resulted in the disaggregation of PML-NB structure. We therefore presume that the cytoplasmic retention of over-expressed Setdb1 occurs as part of a regulatory mechanism to set a tight limit on the nuclear activity of Setdb1, whose excess activity might result in random and haphazard chromatin modifications that cause globally aberrant gene expression. |
ISSN | 1356-9597 |
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Registered Date |
2019-05-02 |
